Review
Biochemistry & Molecular Biology
Andrew Manley, Bahar I. Meshkat, Monica M. Jablonski, T. J. Hollingsworth
Summary: Inherited retinal dystrophies (IRDs) are congenital retinal degenerative diseases with various inheritance patterns caused by defects in retinal function, development, or both. Mutated genes associated with IRDs produce altered protein products that disrupt pathways critical to vision. This manuscript provides a comprehensive review of the molecular mechanisms underlying IRD pathogenesis by examining the genes, protein products, and pathways affected by genetic mutation.
Article
Ophthalmology
Amithavikram R. Hathibelagal, Shrikant R. Bharadwaj, Subhadra Jalali, Ahalya Subramanian, John L. Barbur
Summary: A new method for assessing rod and cone sensitivity was studied, indicating that cone-specific deficits were larger than rod-specific deficits in cone-dominated diseases, while rod-specific deficits were larger than cone-specific deficits in rod-dominated disease. This suggests that this new testing method could be valuable in detecting specific rod/cone losses without the need for dark adaptation.
OPHTHALMIC AND PHYSIOLOGICAL OPTICS
(2021)
Article
Ophthalmology
Yuhong Chen, Jieqiong Chen, Hong Wang, Yang Yu, Wenqiu Wang, Wenjia Liu, Suqin Yu, Yuanyuan Gong, Huixun Jia, Tong Li, Xiaodong Sun
Summary: The prevalence of outer retinal tubulation (ORT) varies among different inherited retinal diseases (IRDs) phenotypes, with the highest prevalence in Bietti crystalline corneoretinal dystrophy (BCD). The presence of choroidal atrophy and inner nuclear layer (INL) cysts may be associated with an increased risk of ORT formation in patients with IRD.
Article
Genetics & Heredity
Ta-Ching Chen, Ding-Siang Huang, Chao-Wen Lin, Chang-Hao Yang, Chung-May Yang, Victoria Y. Wang, Jou-Wei Lin, Allen Chilun Luo, Fung-Rong Hu, Pei-Lung Chen
Summary: A cohort study on inherited retinal degenerations (IRDs) in Taiwan revealed ABCA4 and CYP4V2 variants as major causes, with certain variants identified as population-specific disease-causing hotspots. Timing of seeking medical help was related to affected genes. This study may help patients and caregivers adopt precision genomic medicine and novel gene therapies in the future.
NPJ GENOMIC MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Natalia Martinez-Gil, Oksana Kutsyr, Agustina Noailles, Laura Fernandez-Sanchez, Lorena Vidal, Xavier Sanchez-Saez, Carla Sanchez-Castillo, Pedro Lax, Nicolas Cuenca, Antonio G. Garcia, Victoria Maneu
Summary: P2X7R and P2X4R play important roles in retinal diseases and their expression increases during disease progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, General & Internal
Yulia Haraguchi, Tsun-Kang Chiang, Minzhong Yu
Summary: Inherited retinal dystrophies are a group of disorders that affect the structure and function of the retina. Electrophysiology testing is a valuable tool for assessing and diagnosing these conditions, as well as guiding disease classification and management.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Genetics & Heredity
Akio Oishi, Kaoru Fujinami, Go Mawatari, Nobuhisa Naoi, Yasuhiro Ikeda, Shinji Ueno, Kazuki Kuniyoshi, Takaaki Hayashi, Hiroyuki Kondo, Atsushi Mizota, Kei Shinoda, Sentaro Kusuhara, Makoto Nakamura, Takeshi Iwata, Akitaka Tsujikawa, Kazushige Tsunoda
Summary: This study reported 40 Japanese patients from 30 families with PRPH2-associated retinal dystrophy and identified 17 distinct pathogenic or likely pathogenic variants using next-generation sequencing. The results demonstrate the genotypic and phenotypic variations of the disease in the Asian cohort, showcasing different phenotypes and ages of onset.
Article
Biochemistry & Molecular Biology
Jie Yan, Alexander Guenter, Soumyaparna Das, Regine Muehlfriedel, Stylianos Michalakis, Kangwei Jiao, Mathias W. Seeliger, Francois Paquet-Durand
Summary: Inherited retinal degenerations (IRDs) are blinding diseases characterized by progressive loss of photoreceptors. The excessive activation of calpain and poly (ADP-ribose) polymerase (PARP) is associated with the pathology of IRDs. Inhibitors of these enzymes have shown promise in preventing photoreceptor cell death. However, the relationship between calpain and PARP in IRDs is still unclear. In this study, organotypic retinal explant cultures were used to investigate the effects of calpain inhibitors, PARP inhibitors, and voltage-gated Ca2+ channel (VGCC) inhibitors on cell death in IRD mice models. The results suggest that PARP acts upstream of calpain and both enzymes are part of the same degenerative pathway in Pde6b-dependent photoreceptor degeneration. Our findings highlight the potential of targeting PARP for therapeutic interventions in IRD-type diseases.
Article
Genetics & Heredity
Jin Kyun Oh, Jose G. Vargas Del Valle, Jose Ronaldo Lima de Carvalho, Young Joo Sun, Sarah R. Levi, Joseph Ryu, Jing Yang, Takayuki Nagasaki, Andres Emanuelli, Nailyn Rasool, Rando Allikmets, Janet R. Sparrow, Natalio J. Izquierdo, Jacque L. Duncan, Vinit B. Mahajan, Stephen H. Tsang
Summary: This study describes the phenotypic findings in three unrelated patients with novel mutations in TTLL5, expanding the understanding of TTLL5-mediated retinal disease. The study suggests that mutations in TTLL5 may not only cause cone-rod and cone dystrophies, but also sectoral retinal dystrophy.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Genetics & Heredity
Dae Joong Ma, Hyun-Seob Lee, Kwangsoo Kim, Seongmin Choi, Insoon Jang, Seo-Ho Cho, Chang Ki Yoon, Eun Kyoung Lee, Hyeong Gon Yu
Summary: This study conducted genetic analysis of IRD patients in Korea using WES, identifying various causative genes and providing important reference for future genetic screening and treatment development.
BMC MEDICAL GENOMICS
(2021)
Article
Cell & Tissue Engineering
Eric D. Jong, Sabiha Hacibekiroglu, Lily Guo, Evan Sawula, Biao Li, Chengjin Li, Margaret T. Ho, Molly S. Shoichet, Valerie A. Wallace, Andras Nagy
Summary: A combined cell and gene therapy was developed for the treatment of retinitis pigmentosa (RP). Human embryonic stem cells (hESCs) were genetically engineered to differentiate into retinal pigment epithelium (hRPE) cells, which were used to protect and preserve photoreceptor cells in mouse models. This study reveals the potential of this therapy for RP treatment and the possibility of using hRPE cells for long-term delivery of therapeutic biologics.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Jan-Philipp Bodenbender, Valerio Marino, Leon Bethge, Katarina Stingl, Tobias B. B. Haack, Saskia Biskup, Susanne Kohl, Laura Kuehlewein, Daniele Dell'Orco, Nicole Weisschuh
Summary: This study analyzed clinical heterogeneity and characterized the underlying biallelic variants in TULP1 in 17 patients. The majority of patients exhibited severe rod-driven inherited retinal degeneration, while a fraction of the patients had cone-driven disease. The findings support the hypothesis that TULP1 variants lead to misfolding and trigger unfolded protein response, resulting in photoreceptor death.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Qing Zhu, Xue Rui, Ya Li, Ya You, Xun-Lun Sheng, Bo Lei
Summary: The study aimed to describe the genetic and clinical features of 17 patients with ABCA4-related inherited retinal degenerations (IRDs) and define the phenotype-genotype correlations. Four novel ABCA4 variants were identified, expanding the spectrum of disease-causing variants in ABCA4 for future genetic counseling.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Shih-Fang Wu, Chih-Yao Lin, Rong-Kung Tsai, Yao-Tseng Wen, Feng-Huei Lin, Chia-Yu Chang, Ching- Shen, Shinn-Zong Lin, Horng-Jyh Harn, Tzyy-Wen Chiou, Chin-San Liu, Yan-Ting Chen, Hong-Lin Su
Summary: Research found that mitochondrial transplantation can moderately attenuate the degeneration of retinal layers in RCS rats. This result was confirmed through histological examination and OCT measurement of retina thickness. VEP analysis showed that the transmission time of electrical signals after mitochondrial transplantation was similar to the normal value. The results suggest that mitochondrial transplantation can improve the degeneration of photoreceptors in RCS rats and have potential for clinical application.
Article
Genetics & Heredity
Xuan Xiao, Lin Ye, Changzheng Chen, Hongmei Zheng, Jiajia Yuan
Summary: Hereditary retinal degeneration (HRD) is an irreversible eye disease with genetic and clinical heterogeneity. Variants in the ABCA4 gene are a common cause of HRD. In this study, we conducted a clinical observation of five HRD patients and analyzed the relationship between genotypes and phenotypes.
CURRENT GENE THERAPY
(2022)
Article
Genetics & Heredity
Katerina S. Kucera, Beth Lincoln Boyea, Brooke Migliore, Sarah Nelson Potter, Veronica R. Robles, Oksana Kutsa, Heidi Cope, Katherine C. Okoniewski, Anne Wheeler, Catherine W. Rehder, Edward C. Smith, Holly L. Peay
Summary: Screening for elevated CK-MM levels in dried blood spots is a feasible method to identify newborns with DMD. Including specific cutoffs, repeat testing, and genetic sequencing can improve the accuracy and sensitivity of screening.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Madeline Currey, Ilana Solomon, Sarah Mcgraw, Jenny Shen, Francisco Munoz, Ernesto Sosa, Vanessa Puello-Lozano, Sam Wing, Lisa Lopez, Michelle Afkhami, Janine Lobello, Szabolcs Szelinger, Stacy W. Gray
Summary: This study conducted qualitative interviews with cancer patients and providers to identify gaps in clinical care and propose care delivery solutions for the return of secondary germline findings. The responses of patients varied depending on the amount of pre-test counseling they received, and providers identified insufficient clinic time as a major barrier to pretest education. Online support tools and standardized pre-test education models were favored by providers. There were differing perspectives on how pre-test education should be integrated into clinical workflows, but agreement on the inclusion of differences between somatic and germline testing, likelihood of medically actionable findings, and the possibility of being referred to a genetics provider.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Kiely N. James, Shimul Chowdhury, Yan Ding, Sergey Batalov, Kelly Watkins, Yong Hyun Kwon, Lucitia Van Der Kraan, Katarzyna Ellsworth, Stephen F. Kingsmore, Lucia Guidugli
Summary: This study used genome sequencing to detect a wide range of copy-number variants (CNVs) and other non-single nucleotide variant/indel variant types. These genetic alterations accounted for 15.8% of reported variants, with deletions being the most common type. The study also found that additional genetic tests were ordered in some cases, but failed to report the variants detected by genome sequencing.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Asem Berkalieva, Nicole R. Kelly, Ashley Fisher, Samuel F. Hohmann, Monisha Sebastin, Miranda Di Biase, Katherine E. Bonini, Priya Marathe, Jacqueline A. Odgis, Sabrina A. Suckiel, Michelle A. Ramos, Rosamond Rhodes, Noura S. Abul-Husn, John M. Greally, Carol R. Horowitz, Melissa P. Wasserstein, Eimear E. Kenny, Bruce D. Gelb, Bart S. Ferket
Summary: The study aims to understand the effects of returning diagnostic sequencing results on clinical actions and economic outcomes for pediatric patients with suspected genetic disorders. The results showed that patients with positive findings were more likely to receive specialist consultation, but there were no significant increases in overall physician services and costs. More large-scale studies are needed to confirm these findings.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Kirstine Stochholm, Camilla Holmgard, Shanlee M. Davis, Claus H. Gravholt, Agnethe Berglund
Summary: This study assessed the incidence, prevalence, and age at diagnosis of individuals with 45,X/46,XY mosaicism and described the associated mortality pattern. The study found an increasing incidence of 45,X/46,XY mosaicism in males and a stable incidence in females. Males were diagnosed at an older age than females. Additionally, 45,X/46,XY mosaicism was associated with increased all-cause mortality.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Yunjia Chen, Ender Karaca, Nathaniel H. Robin, Dana Goodloe, Ali Al-Beshri, S. Joy Dean, Anna C. E. Hurst, Andrew J. Carroll, Fady M. Mikhail
Summary: This study confirms the association between DLG2 intragenic deletions and neurodevelopmental disorders, supports the haploinsufficiency of the DLG2 gene, and suggests a potential association between these deletions and congenital anomalies and dysmorphism.
GENETICS IN MEDICINE
(2024)